Prostate cancer is the most commonly diagnosed cancer in males and one of the leading causes of cancer death in the United States. The most common therapeutic option for prostate cancer is androgen ablation, via surgical or medical castration, and chemotherapy because early tumors are androgen dependent. Another option is treatment with antiandrogens (androgenantagonists), which can block the androgen receptor-mediated gene transactivation. Therefore, in current treatments, steroidal antiandrogensare applied. However, advanced prostate cancer is resilient to most treatments. Thus, more effective therapies that can cure localized tumors and prevent their metastasis are urgently needed.
Garcinia species (Family Guttiferae) are tropical evergreen trees and shrubs that are widely distributed in Southeastern Asia and their phytochemistry has been widely studied. Classic and caged xanthones have been isolated from various parts of these plants, and identified as their major bioactive components. Traditionally, Garcinia resin (called gamboge) has been used in folk and Chinese medicine to promote detoxification and treat inflammation and wounds, and recently xanthones isolated from various Garcinia species also showed antibacterial, antioxidant, antiviral and neuroprotective effects.
In the last decade, most of the research on Garcinia species has focused on the anticancer activity of gambogic acid (GA), a caged xanthone found at high concentrations in gamboge. GA has been involved in the injectable antitumor drug since the 1970s. In 2004, GA has been granted permission for testing in clinical trial as a wide spectrum antitumor drug. GA and its derivatives are cytotoxic in many cancer cell lines by binding to the transferrin receptor and induction of G2/M cell cycle arrest and mitochondrial and death receptor-mediated apoptosis. GA also reduces invasion and angiogenesis, telomerase mRNA expression and activity and tumor volume in vivo. However, the antitumor effect of GA is not selective and it induces toxicity to the liver and kidney, which limits its development into a clinically useful anticancer drug.
Due to the toxicity of GA, there is a present need in the art to focus on the discovery of more selective compounds isolated from various Garcinia species.
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